About

Robert Bronstein, PhD, is a Research Assistant Professor of Medicine at Stony Brook University within the Department of Medicine, Division of Nephrology and Hypertension. His research focus is on nephrology and hypertension, contributing to the academic and clinical understanding of kidney-related health issues. As a faculty member, he is involved in advancing research in these areas, supporting the department's mission to improve patient care through scientific investigation.

Research topics

• Endocrinology
• Biology
• Medicine
• Neuroscience
• Cell biology
• Pathology
• Genetics
• Immunology
• Internal medicine

Selected publications

• Patients with major depressive disorder and undiagnosed depression are at risk for inferior outcomes after patellar stabilization surgery

  Journal of ISAKOS Joint Disorders & Orthopaedic Sports Medicine · 2026-02-08

  articleOpen access

  INTRODUCTION/OBJECTIVES: Medial patellofemoral ligament reconstruction (MPFL-R) is commonly performed in patients with recurrent patellar dislocations and associated instability. However, there is limited information on the effects of underlying mental health conditions, such as major depressive disorder (MDD), on operative outcomes. This study assesses how mental health disorders, such as MDD or unrecognized depression, can affect pre- and post-operative outcomes in patients undergoing MPFL-R. METHODS: A retrospective analysis of patients who underwent MPFL-R from 2015 to 2023 was performed. Demographic data, presence of diagnosed mental health disorders, and pre- and post-operative Patient Reported Outcomes Measurement Information Systems (PROMIS) scores were collected. Exclusion criteria included patients aged <10 or >75 years, or those with incomplete PROMIS data. Patients without a formal diagnosis of MDD, but with a preoperative PROMIS-depression T-score ≥52.5 were considered undiagnosed/PROMIS-depressed. RESULTS: 187 patients who met inclusion criteria. Patients with a mental health disorder were more likely to have an underlying connective tissue disease and to require longer follow-up (512 vs 713 days, p < 0.05). A mental health disorder led to significantly worse pre-and post-operative PROMIS depression, physical function, and pain interference scores. The MDD and PROMIS-depressed patients reported significantly worse pre- and post-operative PROMIS scores, with those who were PROMIS-depressed performing particularly worse compared to those without underlying mental health disorders. Odds of achieving Minimal Clinically Important Difference (MCID) were similar across all cohorts. Regression analysis showed an association between underlying mental health disorders or PROMIS-depression with worse average PROMIS scores. CONCLUSION: Patients with underlying mental health disorders may still significantly benefit from MPFL-R compared to their unaffected counterparts, but will nonetheless report worse pre- and post-operative PROMIS scores. Overall, our cohort improved with surgery, but both diagnosed and undiagnosed MDD may still adversely affect patients undergoing MPFL-R. These findings highlight the importance of identifying and addressing mental health issues in this patient population. LEVEL OF EVIDENCE: Level III.

  PublisherOA PDFDOI

• Loss of Snhg5 disrupts cell-cycle regulation without altering cystogenesis in a mouse model of polycystic kidney disease

  Scientific Reports · 2026-01-08

  articleOpen access

  Long non-coding RNAs (lncRNAs) regulate diverse cellular pathways and are increasingly linked to human disease. Snhg5 is frequently described as a pathogenic lncRNA in many human diseases, including cancer. Our previous studies revealed that Snhg5 is one of the most upregulated lncRNAs in multiple mouse models of polycystic kidney disease (PKD). Yet its role in renal biology and in autosomal dominant PKD (ADPKD) is not known. To elucidate the role of Snhg5, we generated a global Snhg5-null mouse. Homozygous animals were viable and displayed normal kidney morphology and function. RNA-sequencing of Snhg5-null kidneys and renal epithelial cells revealed common alterations in gene expression linked to cell cycle progression and DNA replication. At the molecular level, Snhg5-null cells showed increased sub-G1 and S/G2/M fractions, coinciding with depletion of ARPC5-a core ARP2/3 subunit-suggesting that reduced ARPC5 may contribute to this phenotype. To determine whether Snhg5 upregulation is pathogenic in mouse PKD, we crossed Snhg5-null mice with a collecting duct-specific Pkd1-mutant mouse model. Loss of Snhg5 did not attenuate cyst formation; if anything, disease severity was mildly but not significantly exacerbated. These findings indicate that Snhg5 modulates cell-cycle control and is dispensable for kidney development and cystogenesis in collecting duct-derived cysts.

  PublisherOA PDFDOI

• Poster 133: Patients With Major Depressive Disorder and Undiagnosed Depression Are at Risk for Inferior Outcomes After MPFL Reconstruction

  Orthopaedic Journal of Sports Medicine · 2025-09-01

  articleOpen access

  Objectives: Medial patellofemoral ligament (MPFL) reconstruction is commonly performed in patients with recurrent patellar dislocations and associated instability. However, though general outcomes and when to perform concomitant surgical procedures such as a tibial tubercle osteotomy (TTO) have been studied, there remains limited information on the effects of underlying mental health conditions on baseline and post-operative outcome measures. Given the rising prevalence and number of undiagnosed number of patients with mental health conditions such as major depressive disorder (MDD), recognition that patients with chronic, recurrent patellar dislocations who require MPFL reconstruction may be at risk for inferior post-operative outcomes if they also have a mental health disorder. The purpose of this study is to assess how mental health disorders such as MDD or unrecognized depression can affect pre- and post-operative outcomes in patients undergoing MPFL. Methods: A retrospective, IRB approved review of patients undergoing MPFL reconstruction from 2015 to 2023 was performed. Demographic data, presence of diagnosed mental health disorders, complications, and Patient Reported Outcomes Measurement Information Systems (PROMIS) scores related to their procedure were collected. Exclusion criteria included patients aged &lt;10 or &gt;75 years, or those with incomplete PROMIS data. Patients without a formal diagnosis of MDD, but with a pre-op PROMIS-Dep score greater than or equal to 52.5 were considered PROMIS-Depressed. Kruskal-Wallis and chi-squared tests were used to compare continuous and categorical cohort descriptive statistics respectively. Logistic and mixed-effects regression were used to investigate the association between PROMIS T-scores and mental health disorders while adjusting for confounding patient and surgical variables. Results: 187 patients met inclusion criteria. Descriptives of cohort variables tabulated by formal mental health disorder assessment are shown in Table 1. Patients with a mental health disorder were more likely to have an underlying connective tissue disease and require longer follow-up (512 vs 713 days, p &lt;0.05). The presence of a mental health disorder led to significantly worse pre-and post-operative PROMIS scores, however there were no differences in the change in PROMIS scores after surgery nor was there a difference in ability to achieve MCID. Relative to patients without any mental health disorder, MDD patients and those PROMIS-depressed reported significantly worse pre- and post-operative PROMIS scores, with those who were PROMIS- depressed particularly doing worse (Figure 1). However, there were no differences in the change in PROMIS scores after surgery (despite depressed and PROMIS-depressed patients having more room for improvement), nor was there a difference in odds of achieving MCID (Figure 2). Regression analysis showed an association between underlying mental health disorders or need for additional procedures and worse average PROMIS scores in all domains. This was also seen with PROMIS-depressed patients, however presence of connective tissue disorders led to worse PROMIS-PI scores in this patient population. In addition, the odds of a reported complication or need to have a contralateral MPFL procedure were higher in patients requiring TTO. Increased age was associated with worse PROMIS-PI and PF scores. Partial correlation of the odds of needing MPFL on the contralateral extremity weakly correlated with lower odds of PROMIS-PI MCID achievement. Conclusions: The most important finding in our study is that underlying mental health disorders do not affect odds of achieving MCID after undergoing MPFL, however they do lead to worse pre- and post-operative PROMIS scores and prevented patients from deriving more improvement from their surgery. This finding was exacerbated in patients who were PROMIS-depressed. Overall, our cohort improved with surgery, but both diagnosed and undiagnosed MDD adversely affects patients who undergo MPFL reconstruction. Requiring a TTO or having an underlying connective tissue disorders may present as additional risk factors. These findings highlight the importance of identifying and addressing mental health in this patient population, especially given the number of patients who did require contralateral MPFL (with subsequently longer recovery times) and therefore may be susceptible to inferior long-term physical function.

  PublisherDOI

• Arthroscopic intra-articular vs. subpectoral biceps tenodesis with concomitant rotator cuff repair leads to equivocal MCID achievement

  JSES International · 2025-02-14 · 1 citations

  articleOpen access

  Background: Pathologies involving the long head of the biceps brachii tendon often accompany rotator cuff tears, contributing to increased physical pain. Disagreement exists in the literature regarding the outcomes of open subpectoral vs. arthroscopic biceps tenodesis during concomitant arthroscopic rotator cuff repair (ARCR), with limited studies assessing Patient-Reported Outcomes Measurement Information System (PROMIS) in this context. This study aims to evaluate a cohort undergoing open subpectoral vs. arthroscopic intra-articular biceps tenodesis with concomitant ARCR, examining differences in PROMIS outcomes and the ability to achieve a minimal clinically important difference (MCID). We hypothesize there is not a significant difference in attaining MCID for PROMIS outcomes between open subpectoral and arthroscopic intra-articular biceps tenodesis during ARCR. Methods: value threshold of <.05. Results: A total of 197 patients were included for final data analysis. 100 patients underwent arthroscopic biceps tenodesis and 97 patients who underwent open biceps tenodesis, with average follow-up 2.39 vs. 2.21 years, respectively. Bivariate analysis showed no significant differences between subpectoral and arthroscopic cohorts in demographic or clinical variables. Both groups exhibited significant improvement at the final follow-up in all three PROMIS domains without statistically significant intergroup differences. Multivariate analysis identified racial and insurance disparities in preoperative scores but not in postoperative outcomes. Logistic regression indicated PROMIS domains and anchor usage predicted MCID, with no significant difference based on biceps tenodesis type. Conclusion: This study suggests that open subpectoral vs. arthroscopic intra-articular biceps tenodesis during concomitant ARCR does not significantly impact PROMIS outcomes or the likelihood of achieving MCID.

  PublisherDOI

• Krüppel-Like Factor 6 Induces RNA Polymerase II Subunit RPB1 to Promote Kidney Injury

  Journal of the American Society of Nephrology · 2025-05-06 · 4 citations

  articleOpen access

  Key Points Single nuclear RNA sequencing after DNA damage–induced AKI identified an injured proximal tubule cluster with high Polr2a (RNA polymerase subunit B1), an RNA polymerase II subunit. POLR2A knockdown in injured cells decreased inflammatory and fibrotic gene expression, dedifferentiation, DNA damage, and cell cycle arrest. RNA polymerase subunit B1 was higher in mice overexpressing transcription factor Krüppel-like factor 6 and associated with worse injury after DNA damage. Background Initial proximal tubule cell injury and dedifferentiation contribute to AKI, and persistent dedifferentiation drives fibrosis and CKD. Proximal tubule–specific knockdown of zinc-finger transcription factor Krüppel-like factor 6 ( Klf6 ) attenuates the AKI to CKD transition. Our aim was to study the early transcriptional mechanisms by which KLF6 induction exacerbates proximal tubular injury and eventual fibrosis. Methods Aristolochic acid I–treated wild-type and KLF6 overexpression mice underwent single nucleus (sn)RNA-seq and single nucleus assay for transposase-accessible chromatin sequencing (acute phase) and assessment of kidney function, injury, and fibrosis (remodeling phase). POLR2A was knocked down in human kidney cells and cell number, gene expression, differentiation, DNA damage, and cell cycle assessed. Kidney sections from fibrotic mouse models and human CKD secondary to aristolochic acid and diabetes were assessed for RNA polymerase subunit B1 (RPB1) expression. Results snRNA-seq identified an injured proximal tubule cluster with high expression of Klf6 and RNA polymerase II subunit a ( Polr2a ) encoding RPB1. After injury, RPB1-positive cells accumulated and were associated with dedifferentiated proximal tubules. POLR2A knockdown in injured cells increased cell death, but reduced inflammatory and fibrotic gene expression, dedifferentiation, DNA damage, and G2/M cell cycle arrest, with a transcriptional switch from long genes to short genes. Single nucleus assay for transposase-accessible chromatin sequencing demonstrated an open chromatin region in Polr2a intron 1 in injured proximal tubule cells, containing a KLF6-binding site. Knockdown of KLF6 reduced POLR2A induction, while proximal tubule–specific KLF6 further increased Polr2a levels after injury. Mice with tubule-specific KLF6 induction had more RPB1-positive proximal tubules and more injury post-AKI. Human kidney samples with DNA damage–induced CKD and diabetic kidney disease also had high POLR2A /RPB1 expression in dedifferentiated proximal tubule cells. Conclusions Prolonged high expression of RPB1 is associated with dedifferentiated proximal tubule cells. Mice overexpressing KLF6 had higher expression of RPB1 and worse kidney injury after DNA damage.

  PublisherDOI

• Podocyte-Specific Deletion of STAT3 in Krüppel-Like Factor 4–Related Experimental Podocytopathy

  Journal of the American Society of Nephrology · 2025-08-29

  articleOpen access

  Key Points Detrimental effects of Krüppel-like factor 4 knockdown in podocytes were eliminated with the inhibition of signal transducer and activator of transcription 3 (STAT3) signaling specifically in podocytes. Human kidney biopsies with renal vasculitis demonstrated a glomerular enrichment of STAT3 downstream genes, which negatively correlated with eGFR. Deconvolution of the bulk RNA-seq from Nephrotic Syndrome Study Network showed an enrichment of STAT3 downstream genes in podocytes as compared with other cell clusters. Background Podocyte loss and parietal epithelial cell activation are features of subtypes of glomerulonephritis and FSGS. We recently reported that the podocyte-specific loss of Krüppel-like factor 4 ( Klf4 ΔPod ) triggers dysregulated glomerular signal transducer and activator of transcription 3 (STAT3) activation, podocyte loss with parietal epithelial cell activation and proliferation, leading to FSGS. Although pharmacologic systemic STAT3 inhibition attenuated this phenotype, it remains unclear whether the detrimental effects of Klf4 loss are primarily a result of dysregulated STAT3 activation intrinsically in podocytes. Methods Mice with the concurrent and conditional knockdown of Stat3 and Klf4 ( Klf4 ΔPod Stat3 ΔPod ) were generated and characterized. Expression arrays from kidney biopsies with various types of glomerular diseases, deposited in Nephroseq, were interrogated for glomerular expression of genes downstream of STAT3 signaling. Cell-specific modulation of STAT3 genes was determined using single-cell RNA sequencing–based proportional cell type deconvolution of bulk RNA-seq obtained from the Nephrotic Syndrome Study Network (NEPTUNE) FSGS and healthy controls. Results Klf4 ΔPod Stat3 ΔPod mice demonstrated no significant podocyte loss, parietal epithelial cell activation and proliferation, FSGS lesions, albuminuria, kidney dysfunction, and tubulointerstitial fibrosis and inflammation compared with the Klf4 ΔPod mice. Klf4 ΔPod Stat3 ΔPod mice also exhibited less glomerular myofibroblasts (+ α -smooth muscle actin) as compared with Klf4 ΔPod mice. Overall survival was restored in Klf4 ΔPod Stat3 ΔPod mice as compared with Klf4 ΔPod mice. Interrogation of expression arrays from human kidney biopsies with renal vasculitis demonstrated a glomerular enrichment of genes involved in canonical STAT3 signaling as compared with healthy controls, which negatively correlated with eGFR. Deconvolution of the bulk RNA-seq data from NEPTUNE showed an enrichment of these STAT3 genes in podocytes as compared with other glomerular cell clusters. Conclusions Collectively, these data demonstrate that inhibiting podocyte-specific STAT3 signaling was sufficient to counter the detrimental effects of Klf4 loss in podocytes and prevented albuminuria, accelerated podocyte loss, activation and proliferation of parietal epithelial cells, FSGS lesions, and kidney failure.

  PublisherDOI

• <i>Fosl2</i> regulates the transition from parietal epithelial cells to myofibroblasts in the kidney

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-12 · 1 citations

  preprintOpen access1st authorCorresponding

  Abstract Activation and proliferation of parietal epithelial cells (PECs), located along the inner rim of Bowman’s capsule, drives disease progression in subtypes of glomerulonephritis and focal segmental glomerulosclerosis. In examining the mechanisms contributing to PEC activation two established mouse models were utilized in this study, nephrotoxic serum nephritis (transient model) and podocyte-specific Klf4 knockout (progressive model). A role for transcription factor FRA2 ( Fosl2 ) was uncovered through single nuclear multiomic approaches relating to the regulation of PEC transcriptional/chromatin dynamics. Co-immunoprecipitation followed by mass spectrometry assessed the FRA2 protein interactome in cultured PECs, revealing a potential role for FRA2 in alternative splicing. Fosl2 expression was then blunted through CRISPR-Cas9 gene editing in cultured PECs, revealing reduced proliferative capacity and the downregulation of myofibroblast markers. In-vivo genetic lineage tracing of PECs after nephrotoxic serum revealed PEC-to-myofibroblast trans-differentiation events. Finally, immunostaining of human kidney biopsies with varied subtypes of glomerulonephritis confirmed Fosl2 expression in activated PECs within crescentic lesions, with single cell deconvolution strategies assigning PEC-skewed proportion ratios to bulk RNA-seq patient data from the NEPTUNE consortium. These results suggest that FRA2 ( Fosl2 ) directs a conserved molecular program of PEC-specific responses in subtypes of glomerulonephritis and focal segmental glomerulosclerosis.

  PublisherDOI

• A Small Molecule Agonist of Krüppel-Like Factor 15 in Proteinuric Kidney Disease

  Journal of the American Society of Nephrology · 2024-08-12 · 6 citations

  articleOpen access

  Key Points A human podocyte-based high-throughput screen identified a novel agonist of Krüppel-like factor 15 (BT503), independent of glucocorticoid signaling. BT503 demonstrated renoprotective effects in three independent proteinuric kidney murine models. BT503 directly binds to inhibitor of nuclear factor kappa-B kinase subunit beta to inhibit NF-κB activation, which, subsequently restores Krüppel-like factor 15 under cell stress. Background Podocyte loss is the major driver of primary glomerular diseases such as FSGS. While systemic glucocorticoids remain the initial and primary therapy for these diseases, high-dose and chronic use of glucocorticoids is riddled with systemic toxicities. Krüppel-like factor 15 (KLF15) is a glucocorticoid-responsive gene, which is essential for the restoration of mature podocyte differentiation markers and stabilization of actin cytoskeleton in the setting of cell stress. Induction of KLF15 attenuates podocyte injury and glomerulosclerosis in the setting of cell stress. Methods A cell-based high-throughput screen with a subsequent structure–activity relationship study was conducted to identify novel agonists of KLF15 in human podocytes. Next, the agonist was tested in cultured human podocytes under cell stress and in three independent proteinuric models (LPS, nephrotoxic serum nephritis, and HIV-1 transgenic mice). A combination of RNA sequencing and molecular modeling with experimental validation was conducted to demonstrate the direct target of the agonist. Results The high-throughput screen with structure–activity relationship study identified BT503, a urea-based compound, as a novel agonist of KLF15, independent of glucocorticoid signaling. BT503 demonstrated protective effects in cultured human podocytes and in three independent proteinuric murine models. Subsequent molecular modeling with experimental validation shows that BT503 targets the inhibitor of nuclear factor kappa-B kinase complex by directly binding to inhibitor of nuclear factor kappa-B kinase subunit beta to inhibit canonical NF-κB signaling, which, in turn, restores KLF15 under cell stress, thereby rescuing podocyte loss and ameliorating kidney injury. Conclusions By developing and validating a cell-based high-throughput screen in human podocytes, we identified a novel agonist for KLF15 with salutary effects in proteinuric murine models through direct inhibition of inhibitor of nuclear factor kappa-B kinase subunit beta kinase activity.

  PublisherDOI

• Podocyte-specific KLF6 primes proximal tubule CaMK1D signaling to attenuate diabetic kidney disease

  Nature Communications · 2024-09-13 · 15 citations

  articleOpen access

  Diabetic kidney disease (DKD) is the main cause of chronic kidney disease worldwide. While injury to the podocytes, visceral epithelial cells that comprise the glomerular filtration barrier, drives albuminuria, proximal tubule (PT) dysfunction is the critical mediator of DKD progression. Here, we report that the podocyte-specific induction of human KLF6, a zinc-finger binding transcription factor, attenuates podocyte loss, PT dysfunction, and eventual interstitial fibrosis in a male murine model of DKD. Utilizing combination of snRNA-seq, snATAC-seq, and tandem mass spectrometry, we demonstrate that podocyte-specific KLF6 triggers the release of secretory ApoJ to activate calcium/calmodulin dependent protein kinase 1D (CaMK1D) signaling in neighboring PT cells. CaMK1D is enriched in the first segment of the PT, proximal to the podocytes, and is critical to attenuating mitochondrial fission and restoring mitochondrial function under diabetic conditions. Targeting podocyte-PT signaling by enhancing ApoJ-CaMK1D might be a key therapeutic strategy in attenuating the progression of DKD.

  PublisherOA PDFDOI

• Rapid Podocyte Loss Triggers Formation of Intercellular Bridges

  Journal of the American Society of Nephrology · 2024-10-01

  article
  PublisherDOI

Frequent coauthors

• Sandeep K. Mallipattu

  36 shared

• Nehaben A. Gujarati

  Stony Brook University

  15 shared

• Yiqing Guo

  Stony Brook University

  12 shared

• Chelsea C. Estrada

  Stony Brook School

  9 shared

• Michael D. Maloney

  University of Rochester

  8 shared

• Stella E. Tsirka

  Stony Brook University

  7 shared

• John P. Goldblatt

  University of Rochester Medical Center

  7 shared

• Nina Cintron Pregosin

  Stony Brook University

  6 shared

Labs

• Nephrology and HypertensionPI

Education

• fellowship sports medicine, Orthopaedics

  University of Rochester School of Medicine and Dentistry

  1993

• residency, Orthopaedic Surgery

  Rutgers New Jersey Medical School

  1992

• M.D.

  Rutgers New Jersey Medical School

  1987

• MS

  Johns Hopkins University Bloomberg School of Public Health

  1983

• AB

  Colgate University

  1981